Tumours could be the ancestors of animals

CANCER remains a formidable foe even 40 years after Richard Nixon officially declared war on it. A new and controversial hypothesis now offers hope that the war can ultimately be won. It suggests tumours have a limited ability to evade modern therapies - a consequence of the idea that cancer is our most distant animal ancestor, a "living fossil" from over 600 million years ago.

Some cancers evolve resistance to a treatment within a few years. One possible explanation for this is that the cells within a tumour act independently, competing with one another via natural selection to evolve therapy-dodging innovations.

Astrobiologists Charles Lineweaver at the Australian National University in Canberra and Paul Davies at Arizona State University in Tempe have an alternative explanation. They say that evidence of basic cellular cooperation within tumours suggests cancers are a throwback from the origin of the animal kingdom - and that any ability to resist modern drugs relies on an ancient and ultimately limited array of survival tactics.

Their hypothesis builds on an old idea that suggests a link between cancer and the origin of multicellular animals, sometime before 600 million years ago. For billions of years before that point, the animals' single-celled ancestors replicated with reckless abandon. Once organisms contained multiple cells, however, replication had to become more restrained, to avoid adverse effects on the organism.

Cancer is thought to be triggered by a malfunction of the genes that try to hold back this uncontrolled replication. But Lineweaver and Davies go further: cancer is not simply linked to the evolution of animals - it was the earliest animals. They believe these organisms had cracked the problem of runaway replication but they still lacked total control over cell growth and proliferation.

The hypothesis helps to explain some of the more unusual features of tumours, says Lineweaver. Some cancer cells build a network of blood vessels, a process known as angiogenesis, to bring nutrients into the tumour - evidence of tumour-wide cooperation. Other cells gain the ability to spread to other tissues, or metastasise, which is difficult to explain if all cancer cells act independently.

Lineweaver and Davies think the genetic toolkit at work in these first animals is buried within all of us. The genes that came later might have tinkered with it, but whenever those later additions malfunction the ancient genes can revert to their initial function.

Consequently, a tumour is not a collection of independently evolving cells, like bacteria, with almost infinite potential to evolve resistance to therapy. It is a group of largely cooperating cells relying on a finite collection of survival strategies that were locked in place over half a billion years ago (Physical Biology, DOI: 10.1088/1478-3975/8/1/015001).

Reactions to Lineweaver and Davies's idea vary from cautious enthusiasm to outright scepticism. Carlo Maley at the University of California in San Francisco, who studies the evolutionary processes at work in cancer, is receptive: "They make a bunch of interesting predictions," he says.

Others are more guarded. It is an "imaginative metaphor", says Mansi Srivastava at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, who studies the evolution of genes including those involved with cancer. However, she thinks the idea of cancer as a living fossil from the dawn of animal life is a step too far. "There is no evidence to believe that the ability to develop blood vessels is an ancient feature of animals."

Lineweaver disagrees: "Fully developed angiogenesis had to have evolved from proto-angiogenesis," he says. "I think it's clear that some form of proto-angiogenesis was very important for the earliest animals."

Genetic profiling may soon help to test the hypothesis, says Lineweaver. The ways a particular cancer responds to treatment in different people should correlate with each other, he says, because they should share strategies for dealing with toxins that were developed in the earliest animals.

Even if cancer does have a limited ability to resist treatment, though, Maley has a reality check. If the war on cancer has taught us anything, it is that battling even a predictable cancer will remain "plenty hard" in the short term.

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.